Basic Principles Of Radiation Therapy, CT, IT & GT In Gynaec Flashcards
Radiobiology of normal tissue
X rays, Gamma rays
RADIOBIOLOGY OF NORMAL TISSUES
The effects of radiation on tissues are generally of two types: (1) Loss of mature functional cells by apoptosis (programmed cell death). This usually occurs within 24 hours of radiation. (2) Loss of cellular reproductive capacity. The severity depends upon the total dose of radiation, length of time over which radiotherapy is delivered and the radiosensitivity of the particular cell types. Usually lost cells are replaced by proliferation of surviving stem cells or progenitor cells.
Ionizing radiation used for therapy may be: (a) Electromagnetic radiation; (b) Particulate radiation.
Electromagnetic Radiation
This consists of quanta of energy and wavelength (photon radiation). They are of two types-X-rays and gamma rays. These electromagnetic waves travels in discrete bundles called ‘photons!
■ Gamma rays are produced spontaneously as a result of decay of the atomic nucleus of some radioactive isotopes. 60 Cobalt or 192 Iridium is a source of y-rays.
■X-rays are produced outside the atomic nucleus. When fast-moving electrons approach the fields around the nuclei of atoms of a target material (tungsten), they are deflected from their path. The energy thus emitted in the form of electromagnetic radiation (photons) is X-rays. Machines such as betatron (circular fashion) and linear accelerator (linear fashion) can accelerate electrons with high kinetic energy. Therefore, X-rays generated by these machines are very high in energy.
■X-rays and gamma rays are collectively called photons. When photons interact with matter (tissue), three effects are observed: (1) Photoelectric effect; (2) Compton scattering; and (3) Pair production. In human radiation therapy, compton scattering is the major interaction of photons with tissue (Fig. 31.1). X-rays and gamma rays have shorter wavelength and high frequency. They have high kinetic energy. X-rays and gamma rays possess considerable power of tissue penetration depending on the photon energy and the density of the matter through which they pass. The photon energy produced from radioactive cobalt is 1.2 million electron volts (MeV). External photon beam radiation is usually derived from a linear accelerator (p. 427).
Principles of Radiation Physics and Radiobiology
■In the treatment of gynecologic malignancy the most common source of radiation is electromagnetic (photon) radiation. Photons are generally referred to as X-rays or gamma rays.
■Radioactive nuclei particles give off alpha and beta particles and gamma rays.
■Radium 226, Cesium 137, Gold 198, Iodine 125, Cobalt 60, Iridium 192 are used as radioactive sources for therapeutic purpose (Table 31.1).
■Radioactive substances are encapsulated to absorb alpha and beta particles leaving gamma rays to attain therapeutic purpose.
■ Oxygen enhancement ratio (OER): The ratio of radiation dose required for a given level of cell killing under hypoxic condition compared with the dose needed in air.
■ Inverse square law: Dose of radiation at a particular point varies inversely proportional to the square of the distance from the source of radiation.
■ Fractional cell kill: Each radiation dose kills a constant fraction of the tumor cells.
■ Radiation dose rate: Large radiation doses per fraction cause the largest number of tumor cell kills; at the same time the large doses may cause maximum damage on normal tissues. Ultimately this is the cause of many early and late complications.
■Radiation resistance: Tumor cells are mostly sensitive to the effects of radiation. This results in tumor regression or tumor repopulation during or after radiation treatment. Radiation resistance associated with (a) rapid cell repair of radiation damage; (b) Active concentration of chemical radio-protectors; or (c) Cellular hypoxia.
■ Cell cycle dependency of cell kill: Actively proliferat- ing tumor cells are most after often killed by radiation therapy. Ionizing radiation has its greatest cell kill effect during the mitotic phase (M phase) and to some extent in the late G-1 phase and in early deoxyribonucleic acid (DNA) synthesis phase.
■ Radiosensitivity:
Particulate Radiation
This consists of atomic subparticles such as electrons, protons, and neutrons. Only electrons (B-rays) are used in radiotherapy.
Techniques of Radiation therapy
Brachytherapy
Brachytherapy
It gives a very high dose of radiation where the source of radiation is placed within, or close to the tumor. The application may be: (a) Intracavitary; (b) Interstitial; or (c) Surface (skin). Damage to normal tissues is less as there is rapid falloff of radiation around the source (inverse
square law).
Intracavitary: The devices for brachytherapy consist of hollow stem (intrauterine tandem), which is placed within the uterine cavity (Fig. 31.2). Specially designed devices used for vaginal placements are called vaginal ovoids or
colpostats. Interstitial: The form of brachytherapy consists of
placement of radioactive sources (needles, wires or seeds) within the tissues. Commonly used sources are Iridium 192 (192Ir), Cesium 137 (137Cs), and Cobalt 60 (60Co). Small volume of tumor, as in early cases of vaginal carcinoma, can be treated with the method. Normal tissues are spared from radiation injury.
Intraperitoneal: Intraperitoneal instillation (32P) is another mode of local therapy.
After loading technique: It is a modern development of brachytherapy to prevent radiation complications to the personnel. A mock insertion of applicators is performed and X-ray is taken to note their exact position. After loading technique may be manual or by remote control. Later on, live radioactive sources are introduced by remote control in identical manner. Remote after loading system uses selectron (137Cs) or high-dose selectron (60Co). Remote control systems allow complete protection of staff from radiation exposure.
Brachytherapy can be either low dose rate (LDR) or a high dose rate (HDR) system. LDR require hospital admission and deliver dose at about 50-100 cGy/hour. HDR systems are commonly done as outpatient basis. The dose rate delivered is at 100 cGy/minute.
Advantages: Localized high radiation dose to a small tumor volume with high local control. Radiation dose in the surrounding normal tissues is less as there is sharp fall off according to inverse square law (see above).
Disadvantages: (a) Large tumors are usually unsuitable unless used following external beam radiation therapy (EBRT) and/or chemotherapy; (b) Risks of exposure to medical and nursing personnel due to gamma rays.
Techniques of Radiation Therapy
External Beam Radiotherapy
External Beam Radiotherapy
External beam radiotherapy (EBRT) or teletherapy is the treatment with beams of ionizing radiation produced from a source external to the patient. Superficial tumors may be treated with X-rays of low energy in the range of 80-300 KV. Deep-seated tumors are usually treated using megavoltage photons.
Cobalt 60 is the common teletherapy source for EBRT, the other one is Cesium 137. External radiation therapy is used to treat large volumes (tumor, lymph nodes, parametrium) of tumor (p. 294). It is designed to deliver a uniform radiation dose to the tumor volume without ‘hot’ (excess dose) or ‘cold’ (under dose) spots. Accurate tumor localization and volume measurement are essential. Greater the tumor volume, higher the radiation dose required.
Instillation of Radioisotopes into the Peritoneal or Pleural Cavity
Radioactive isotopes of either gold or phosphorus, linked to carrier colloids, are commonly used in ovarian cancer. This can give radiation only to a depth of 4-8 mm. Radioactive chromic phosphate (32P) emits pure ẞ-rays and has got longer half-life (14.3 days) and deeper penetration (8 mm) power compared to radio gold (198 Au). Small volume of tumor in the peritoneal or pleural cavity is treated with solution of radioisotopes.
Palliative radiotherapy is aimed to achieve quick symptom control. It may have little or no impact on the survival outcome of the patient. Lowest dose of therapy is preferred so that normal tissue damage is avoided.
Measurements of Radiation?
MEASUREMENT OF RADIATION
Radiation absorption dose (Gray) is the unit used to measure the amount of energy absorbed per unit mass of tissue. One gray (Gy) is equivalent to 1 Joule/kg which is equivalent to 100 rads. Currently, the term centigray (cGy) is used. One cGy is equivalent to one rad. Amount of radiation the patient receives is calculated by dosimetry. Homogeneous irradiation of tissues is desirable (Fig. 31.2). Primary tumor should receive high dose. Brachytherapy and teletherapy should be combined to provide adequate irradiation to the primary tumor as well as the pelvic lymph nodes and the parametrium (Fig. 31.3).
Biological effects of Radiation (Radiobiology)
Biological Effects of Radiation (Radiobiology)
Radiation has got two modes of action:
- Direct action: Where the radiation is absorbed, it causes damage to DNA directly. This is the predominant mechanism of action of particulate radiation (neutrons).
- Indirect action: Where the radiation interact with other substances (H₂O) in the cell to produce free radicals (OH-) which in turn damages the DNA.
Radiation, depending on the dose and time of exposure may cause (a) gene mutation; (b) abnormal cell mitosis; and (c) derangement of reproductive ability of the cell-‘progeria.
Compton effect produces fast electrons by dislodging orbital electrons of tissues, through which they pass. This fast electron ionizes molecules along its path. There is production of free hydrogen atoms, free hydroxyl radicals, and H₂O₂. These ionized molecules react with proteins, enzymes, and nucleic acids resulting in structural and functional alteration of a cell.
The target for radiation injury is DNA. Ultimately, there is limited cell mitosis and mitotic cell death. There is cytoplasmic vacuolation and fragmentation. Ionizing radiation also produces damage to nuclear and plasma membranes.
This effect of ionizing radiation is common for both the normal and neoplastic tissues, encountered in the radiation path. Radiation complications are mainly due to interaction with the normal tissues (Table 31.2). When the radiation effect to a cell is sublethal, cellular DNA may undergo repair and the cell survives. Lethal effect kills the cell.
Radiation Dose
Radiocurability
Radiation reactions and their management(image).
Radiation Dose
According to the ‘inverse square law’ there is reduction of radiation at a distance from the source in brachytherapy. This protects the normal tissues (isodose distribution curve, Fig. 31.2).
A planning computer calculates the field sizes, the dose from each field and the angles of the treatment machine. High energy machines spare the skin and deliver more radiation below the skin surface. Linear accelerators which deliver X-rays of 4-8 MeV are used currently. Treatment is carried out in a especially protected room. During the treatment time, the patient should be alone and he/she is supervised using a television camera. Safety precautions of radiation are maintained.
Radiocurability is the elimination of tumor at the primary or metastatic site due to a direct effect of radiation.
Radiosensitivity
Definition:
Highly Sensitive
Moderately Sensitive
Poorly Sensitive
Radiosensitivity depends on which factors
Fractionation?
Radiosensitivity means the response of the tumor to irradiation. Radiosensitivity is measured in terms of loss of cellular proliferative capacity due to the damage to DNA. Accumulation of sublethal injury following repeat radiation leads to ultimate DNA damage and cell death. Radiosensitivity varies with the type of cancer.
a. Highly sensitive: Dysgerminoma, embryonal cancer, small cell cancer and lymphoma.
b. Moderately sensitive: Squamous cell cancer, adeno- carcinoma.
c. Poorly sensitive: Melanoma, glioma
Radiosensitivity depends on several factors.
■Tissue hypoxia: Higher the hypoxic fraction of cells, the less (2-3 times) is the radiation response. Hypoxic cells are more resistant to radiation compared to toxic cells.
■Proportion of mitotic (clonogenic) cells: Clonogenic cells are more radiosensitive.
■Cell cycle: Mitotic cells (M phase) and G2 cells are more radiosensitive compared to late S-phase cells (Fig. 31.4).
Tumor specificity: Certain tumors (dysgerminomas) are more radiosensitive than the others.
■Tumor volume: Smaller the tumor volume → lesser the hypoxic cells less the radiation dose better the radiation response.
Lesser the photon wavelength more is the penetrating power and energy of ionizing radiation. Supervoltage and megavoltage radiation (6⁰CO, 137Cs, 226Ra, betatron, linear accelerator) have the following advantages over the orthovoltage one. They have higher energy of radiation, less skin injury, less lateral scattering, and more tissue penetration at a greater depth. They are suitable for the deep seated tumors (e.g. carcinomas of the cervix and endometrium).
Fractionation is the division of a total dose of external beam radiotherapy into small (daily) doses. Thus it spares normal tissue damage preferentially. External beam radiotherapy is usually fractionated and is given once daily for five times a week. A dose of 180-220 cGy per fraction is used. This is based on the ability of the cells to accumulate and repair the sublethal injury. Tumor tissue takes longer time to recover from radiation damage compared to normal tissue. Fractionation allows normal tissue (intestinal mucosa, bone marrow) to repair sublethal injury (sparing effect). On the other hand irradiation results in accumulation of sublethal damage and ultimate loss of reproductive capacity in tumor tissue.
Radiation dose prescription should include the total dose, number of fractions with dose and time for each fraction (e.g. 40 Gy in 20 fractions given five times weekly can be completed in 4 weeks at 2 Gy per fraction).
Advances in Radiation Therapy
ADVANCES IN RADIATION THERAPY
High linear energy transfer: X-rays and y-rays are less effective against hypoxic cells compared to oxygenated cells. Fast neutrons or negative a mesons (pions) or protons are very effective against the hypoxic cells. Fast neutron beam for radiotherapy are generated by the cyclotron and the D-T generator. The neutron is emitted with an energy of 14-16 MeV.
Negative a mesons (pions) with energies between 40 and 70 MeV have a depth range in tissue of about 6-13 cm. It has high biologic effectiveness and a low dependence on oxygen.
Radiopotentiators and Hypoxic Cell Sensitizers
RADIOPOTENTIATORS AND HYPOXIC CELL SENSITIZERS
Compared to well-oxygenated cells, hypoxic cells require about three times the radiation dose, to obtain the same proportion of cell kill. Hypoxic cell can be sensitized to ionizing radiation to improve the oxygen enhancement ratio (OER) by different chemical compounds.
Number of chemotherapeutic agents have been found to potentiate the radiation effect and also to sensitize the hypoxic cells (Table 31.3). Exact mechanism is not well-understood. Use of hyperbaric oxygen to increase radiosensitivity is of doubtful benefit. Moreover this technique is cumbersome.
Intraoperative radiation of large fraction of 1500- 2500 cGy are delivered directly to the area selected. Periaortic node irradiation (biopsy proven) at the time of staging laparotomy is possible.
Hyperthermia is found helpful as an active anti- neoplastic agent and a significant radiosensitizer.
TABLE 31.3: Radiopotentiators, hypoxic cell sensitizers.
Chemotherapeutic agents
■ Cisplatin
■ Paclitaxel
■ Gemcitabine
■Doxorubicin
Others
■ Metronidazole
■ Tumor necrosis factor (TNF)
■ Interferon
■ Acyclovir
New Technologies for Radiation Therapy
Three-dimensional Conformal Radiation Therapy (3D CRT)
3D CRT uses imaging modalities (CT, MRI, and PET scanning). Beam placement using a CT simulation is used. 3D conformal radiotherapy (3D CRT) can shape the beam to conform to the target. Computerized dosimetry is currently used. This can help to arrange the beams to maximize dose to the tumor and minimize dose to normal tissues (Table 31.4).
Intensity Modulated Radiation Therapy (IMRT)
IMRT uses the power of computers to shape and perform thousands of iterations of planning to maximize the tumor dose and to minimize normal tissue dose. Both 3D CRT and IMRT use small collimator “leaves” to shape the beam finely. These “leaves” are mobile and can vary the beam intensity. It allows irregular shapes (tumor) to be treated and has the benefit of reduced radiation to normal tissues (bowel, bladder).
Tomotherapy and cone-beam CT may allow more precise localization of beam and verification of dose delivered.
Stereotactic Radiotherapy and Gamma Knife
Radiation
The are similar to IMRT and 3D CRT to allow precise high dose delivery of external radiation. Stereoatactic radiation uses a modification of linear accelerator
Treatment field of Carcinoma Cervix
Treatment Field for Carcinoma Cervix
Superior border-between L₁ and L, to include the common iliac nodes. Inferior border-2 cm below the inferior margin of obturator foramen to include the obturator nodes. Lateral borders-1.5-2 cm lateral to the margins of the pelvic brim.
Lead compensators are used in the path of external beam radiation to prevent overdose to the central portion of the pelvis, which has received high dosage from brachytherapy.
Radiotherapy in Epithelial Ovarian Carcinoma
Radiotherapy in Epithelial Ovarian Carcinoma
Chemotherapy has replaced radiotherapy both for the management of early and advanced disease. However, it may be used in the following cases who fail to respond with chemotherapy: (a) Metastatic deposits over the peritoneal surfaces; (b) Lymph node metastasis; (c) Palliation for painful recurrences in the pelvis or bone.
Moving strip technique is used to irradiate whole of abdomen. Presence of residual disease following debulking procedures in a case of ovarian carcinoma is treated with this technique. Whole abdomen is divided into contiguous strips of 2.5 cm wide area. Each strip is irradiated from front and back over 2 days and the field is gradually moved up. Cobalt 60 machine is generally used and a total tumor dose of 2600-2800 cGy is delivered. Pelvic boost of 2000-3000 cGy is given additionally. Kidneys and right lobe of liver are shielded with lead to reduce the dose to these organs. Bulky residual disease (>2 cm) is not suitable for radiotherapy.
Use of radiotherapy for individual organ malignancy- see respective Chapters.
Radiation reactions and their management-see Table 31.2. Contraindications of radiotherapy-p. 292.
Tissue tolerance of Radiation Dose
